The present invention relates to a method of efficiently separating and recovering 18F contained in 18O water.
The positron emitting nuclides used in positron emission tomography (PET) include 11C (half-life of 20 min), 13N (10 min), 15O (2 min), and 18F (110 min), and of these 11C and 18F are most widely used. They have a short average lifetime and can be manufactured, in principle, without carriers. To utilize these short-lifetime nuclides, an accelerator is set up near the relevant facility. Since, particularly, 18F has a relatively long-lifetime (half-life of 110 min), there are expectations for its application in research and medical facilities located away from the accelerator facility. The longer lifetime also allows to take time in synthesizing a labeled compound, and vigorous attempts are being made to synthesize a variety of labeled compounds. A labeled compound 18FDG is used not only as a tracer in measuring saccharometabolism in the brain but also as an imaging agent for cancer tumors. Metastasis of cancer cells, for example, can be detected with higher sensitivity by PET than by X-ray CT or MRT. 18F-DOPA is used for diagnosing Parkinson""s disease.
18F is produced through the 18O(p, n)18F reaction by irradiating a liquid target 18O water with protons. Only a minute amount of 18O produces a nuclear reaction. 18O water is expensive, and since a few grams of it is required for a single irradiation, efficient recovery and reuse of 18O is strongly called for in order to reduce running costs. A conventional 18F recovery method is based on the use of an ion exchange resin. The method consists of a two-step operation, in which 18F is separated from 18O water by ion exchange, and then 18F is recovered from the ion exchange resin by using, e.g., carbon dioxide gas or potassium carbonate. The ion exchange resin must be carefully processed beforehand, and caution must be exercised so as to prevent the mixing of chlorine ions. While chemicals (carbon dioxide gas, potassium carbonate and the like) are used for recovery of 18F adsorbed on the ion exchange resin, these impurities are not desirable from the viewpoint of having greater possibilities for the synthesis of labeled compounds. There are also the problems regarding the control of flow rate of a 18F solvent for ion exchange and the clogging of the ion exchange resin column.
Alexoff et al have performed 18F-electrodeposition experiments in search of a method of recovering 18F alternative to the ion exchange resin method (Appl. Radiat. Isot. Vol. 40, No. 1, pp.1-6, 1989). They examined the time, voltage and electric field gradient dependence of the electrodeposition rate and recovery rate. The recovery rate of 18F was 70% (rate of electrodeposition on a vitreous carbon electrode surface was 95%, and the ratio of re-emission of 18F was 70%), which did not reach the recovery rate (95%) in the case of using an ion exchange resin. Further, when the voltage was increased, vitreous carbon powder dropped into the liquid solution. The authors conclude, therefore, that while the electrodeposition method can recover 18F that does not contain impurities, the ion exchange resin method is superior for the purpose of recovering greater-strength 18F required for PET.
A high recovery rate is required in recovering the 18F that is produced through the nuclear reaction 18O(p, n)18F by irradiating a liquid target 18O water with protons accelerated by a cyclotron. 18F used for the synthesis of labeled compounds for medical or biological experiment purposes requires a particularly high purity. The half-life of 18F, though longer than that of, e.g., 11C (half-life 20 min), is only 110 min. Accordingly, the recovery of 18F and synthesis of labeled compounds using 18F must be finished in a short period of time. It is also important to recover the 18O water at high purity after the separation and recovery of 18F, so that the 18O water can be reused and the running cost of 18F manufacture for PET can be minimized.
The present invention takes advantage of the electrolysis method to avoid the problems of the ion exchange resin method, and has as its object the realization of highly efficient recovery of 18F and high-purity 18O water.
In accordance with the present invention, 18F in 18O water held in a container is electrodeposited on the surface of a solid electrode which is used as an anode. The electrodeposition liquid (18O water) remaining after the electrodeposition of 18F is recycled for irradiation. By using, as a cathode, the solid electrode on which 18F has been electrodeposited and, as an anode, a container holding pure water or an electrode disposed in the container with the pure water, a voltage of opposite polarity to the case of electrodeposition is applied. As a result, the 18F electrodeposited on the solid electrode is desorbed into the pure water and recovered as an 18F solution. By using high-purity graphite or platinum as the solid electrode, mixing of impurities, which blocks the synthesis and use of labeled compounds, can be prevented in the recovery process.
Further, by controlling the value of voltage or current for the electrodeposition and desorption of 18F, the efficiency of electrodeposition and desorption are controlled. This method solves the problems of the electrodeposition methods according to the prior art, and enables a high-purity 18F to be recovered at high efficiency while maintaining the purity of the expensive 18O water.
Specifically, the method of separating and recovering 18F according to the present invention comprises the steps of: applying a voltage by using a solid electrode as an anode and, as a cathode, either an electrode disposed in a container holding 18O water containing 18F or the container itself, such that the 18F binds to the surface of the solid electrode; and applying a voltage by using the solid electrode to which the 18F has bound as a cathode and, as an anode, either an electrode disposed in a container holding pure water or the pure-water holding container itself, such that the 18F bound to the surface of the solid electrode is released into the pure water. The container for holding the 18O water containing 18F and the container for holding pure water may be one and the same or separate.
The solid electrode may use either carbon or platinum. For the recovery of a high-intensity 18F, it is preferable to use graphite as a carbon member, or platinum which is meshed or made porous to increase its surface area.
During the step of having the 18F bind to the solid electrode surface, the progress of electrodeposition of 18F to the solid electrode surface may be monitored on the basis of an electric current (electrodeposition current) flowing between the anode and the cathode. The electrodeposition current initially exhibits a large value but this gradually decreases, and becomes constant when most of the 18F in the solution has been electrodeposited on the surface of the solid electrode. Thus, the changes in the electrodeposition current can be measured so that the time at which the current becomes constant can be regarded as the time at which electrodeposition comes to an end.
Similarly, the step of releasing the 18F bound to the surface of the solid electrode into the pure water may comprise monitoring the degree of release of 18F into pure water on the basis of either the current (desorption current) flowing between the solid electrode (cathode) and the anode, or the voltage (desorption voltage) across the solid electrode (cathode) and the anode, or both. For example, the current flowing between the solid electrode and the anode increases as 18F is released into pure water, but the rate of increase slows down and the current approaches a constant value as the release of 18F approaches an end. Thus, the current flowing between the solid electrode and the anode can be monitored so that the step of releasing 18F can be stopped when the current reaches a constant value.
Thus, by monitoring the electrodeposition current, the desorption current, or the release voltage, the degree or progress of electrodeposition or desorption of 18F can be known, so that time loss can be eliminated.
By controlling the current or voltage, the rate of electrodeposition and desorption of 18F can be controlled. As a result, excessive generation of heat can be prevented so that, when a carbon electrode is used as the solid electrode, the peeling of the carbon electrode caused by heating can be prevented. Further, by controlling the size of the solid electrode, the efficiency of electrodeposition and desorption can be improved. It should be noted that, in the case where an electrolyte is used for the synthesis of 18F-labeled compounds, the time required for releasing may possibly be reduced by mixing the electrolyte into the desorbed liquid and thus increasing the electric conductivity.
In accordance with the present invention, since the 18F in the 18O water is removed by binding it to the surface of the solid electrode, the 18O water is not diluted nor are impurities mixed therein during the process of recovering 18F. Further, it was found that the electrodeposition current increases as the activity of 18F becomes greater. This means that in the case of electrodepositing a high-intensity 18F, there is no need to add Na19F as an electric charge carrier for electrodeposition. Thus, since the method of the present invention does not involve the impurity Na19F, a high-purity 18O water can be easily recovered.
Furthermore, in the case where a Havar foil is used for the 18O water target container for the proton irradiation, radioactive metal ions (isotopes of Co, Mn and the like) that are produced through a nuclear reaction by proton irradiation and recoiled into the solution can be eliminated during the 18F-electrodeposition and recovery process (see FIG. 8). All the metal ions such as 48V produced in case a Ti foil is used for the target container, metal ions contained in the 18O water as impurities, and nonradioactive metal ions eluting from other containers, liquid-delivery pump, tubes and the like, can be eliminated. The radioactive metal ion must be eliminated because it is not only harmful to the human body, but it also lowers, together with the stable metal ion, the efficiency with which 18F-labeled compounds are synthesized.
In contrast to the conventional ion exchange resin methods, the method of the present invention does not employ an ion exchange resin. Thus, the method of the present invention does not require a pre-treatment of the ion exchange resin and a flow-rate control of 18F solution for ion exchange, and does not suffer from the clogging of the ion exchange resin column. The column is disposed of as a radioactive waste after a single use, but an electrodeposition method only requires a replacement of the carbon electrode. Moreover, there is no need to use chemicals for recovery. Thus, the method of the present invention can prevent the mixing of impurities and also allows labeled compounds to be easily synthesized.